Evaluation of two family-based intervention programs for children affected by rare disease and their families - research network (CARE-FAM-NET): study protocol for a rater-blinded, randomized, controlled, multicenter trial in a 2x2 factorial design.

BACKGROUND: Families of children with rare diseases (i.e., not more than 5 out of 10,000 people are affected) are often highly burdened with fears, insecurities and concerns regarding the affected child and its siblings. Although families caring for children with rare diseases are known to be at risk for mental disorders, the evaluation of special programs under high methodological standards has not been conducted so far. Moreover, the implementation of interventions for this group into regular care has not yet been accomplished in Germany. The efficacy and cost-effectiveness of a family-based intervention will be assessed. METHODS/DESIGN: The study is a 2x2 factorial randomized controlled multicenter trial conducted at 17 study centers throughout Germany. Participants are families with children and adolescents affected by a rare disease aged 0 to 21 years. Families in the face-to-face intervention CARE-FAM, online intervention WEP-CARE or the combination of both will be treated over a period of roughly 6 months. Topics discussed in the interventions include coping, family relations, and social support. Families in the control condition will receive treatment as usual. The primary efficacy outcome is parental mental health, measured by the Structured Clinical Interview for DSM-IV (SCID-I) by blinded external raters. Further outcomes will be assessed from the parents' as well as the children's perspective. Participants are investigated at baseline, 6, 12 and 18 months after randomization. In addition to the assessment of various psychosocial outcomes, a comprehensive health-economic evaluation will be performed. DISCUSSION: This paper describes the implementation and evaluation of two family-based intervention programs for Children Affected by Rare Disease and their Family's Network (CARE-FAM-NET) in German standard care. A methodologically challenging study design is used to reflect the complexity of the actual medical care situation. This trial could be an important contribution to the improvement of care for this highly burdened group. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00015859 (registered 18 December 2018) and ClinicalTrials.gov : NCT04339465 (registered 8 April 2020). Protocol Version: 15 August 2020 (Version 6.1). Trial status: Recruitment started on 1 January 2019 and will be completed on 31 March 2021.

[Health Science Research with Primary Care Routine Data From Electronic Patient Records: the BeoNet Registry]. / Gesundheitswissenschaftliche Forschung mit primärärztlichen Routinedaten der elektronischen Patientenakte: das BeoNet-Register.

Reliable current information is needed for daily patient care and the health system, but comprehensive data, especially from primary care, are scarce and/or hard to access. The BeoNet Register-Database (BNR) aims to depict quality of medical care in Germany using routine data and with no additional documentation or costs for GPs. Registry design, data structure and database use will be demonstrated using chronic obstructive lung disease (COPD) as an example. The BNR is moving through pilot- and roll-out phases. Participating practices provide standardized information about (1) master data (2) practice profile (3) infrastructure and documentation systems. The routinely documented data will be pseudonymized before transmission via standardized secure interfaces to the registry database. Practices can participate in studies in cooperation with BNR if informed consent is obtained from the patients. The registry data will be linked with questionnaires on health care utilization, quality of life and disease-specific parameters. Researchers and physicians can access quasi anonymized data in specific datasets extracted from the registry. Regular automatic data quality checks and feedback from GPs, patients and researchers enhance the quality of the registry. Performance and data analysis are continuously optimized. The data security concept has been approved and ethical approval is on hand. GPs, pediatricians and pneumologists from Hanover, Munich and Heidelberg participated in the pilot phase. The registry database currently holds 98497 patient IDs and related information. BNR contains more than the standard billing data collected by health insurers. The data are applicable to a wide range of health practices, health care and economics and disease development questions. Questionnaires have been generated, tested and are being distributed. First descriptive analyses of prevalence, age and gender have been performed. Quality and validity checks have been implemented. 2016 marks the roll-out phase of the BNR. Further recruitment of practices throughout Germany, data linkage with additional questionnaires, recruitment of patients for health care research projects, quality checks and data analysis of disease-specific costs and health-related quality of life in COPD are progressing with the overall aim of improving pulmonary healthcare strategies. The floor is now open for retro- and prospective cross-sectional and longitudinal studies.

Valuation of the EQ-5D-5L with composite time trade-off for the German population - an exploratory study.

BACKGROUND: The EuroQol Group has extended the severity levels of the EQ-5D from three to five (EQ-5D-5L). There are valuation studies worldwide planned in order to convert the EQ-5D-5L health states into a single preference-based summary score based on country-specific value sets of social health status preference valuations. The EuroQol Group developed an internationally standardised EQ-5D-5L valuation protocol. Based on the experiences of the first wave of valuation studies applying the protocol, a number of modifications to the implementation of composite time trade-off (cTTO) were proposed and tested in an exploratory study in Germany. METHODS: The aim of the study is to test the improved EQ-5D-5L valuation protocol 1.1 and the implementation of three modifications: (1) introduction of ranking task, (2) separating time trade-off (TTO) tasks for health states "Better Than Dead"(BTD)/"Worse Than Dead" (WTD), (3) allow for removal of problematic valuations from the cTTO data (the feedback module). Data were collected in computer assisted personal interviews with 200 members of the German general public. RESULTS: In comparison to the first wave of valuation studies a higher data quality can be observed in both study arms: increasing number of WTD valuations, reduced inconsistencies for health state 55555 as well as higher values for mild health states. Comparing both study arms, mean observed cTTO value for severity 6 is higher in the test arm. The proportion of inconsistent cTTO responses is lower in the test arm than in the control arm and is further reduced by the feedback module. The ranking task prolongs the interview without the desired effect. CONCLUSIONS: Both study arms yielded higher data quality in comparison to the first wave of EQ-5D-5L valuation studies. The valuation protocol combined with an intensive interviewer training and close data monitoring showed a high feasibility and acceptability to the respondents of the general population as well as the interviewers in Germany. Based on the results of this study and other countries, the separation of TTO tasks for health states BTD/WTD and the feedback module will be implemented in the valuation study for the EQ-5D-5L for Germany.

Comparison of different approaches applied in Analytic Hierarchy Process - an example of information needs of patients with rare diseases.

BACKGROUND: The Analytic Hierarchy Process (AHP) is increasingly used to measure patient priorities. Studies have shown that there are several different approaches to data acquisition and data aggregation. The aim of this study was to measure the information needs of patients having a rare disease and to analyze the effects of these different AHP approaches. The ranking of information needs is then used to display information categories on a web-based information portal about rare diseases according to the patient's priorities. METHODS: The information needs of patients suffering from rare diseases were identified by an Internet research study and a preliminary qualitative study. Hence, we designed a three-level hierarchy containing 13 criteria. For data acquisition, the differences in outcomes were investigated using individual versus group judgements separately. Furthermore, we analyzed the different effects when using the median and arithmetic and geometric means for data aggregation. A consistency ratio ≤0.2 was determined to represent an acceptable consistency level. RESULTS: Forty individual and three group judgements were collected from patients suffering from a rare disease and their close relatives. The consistency ratio of 31 individual and three group judgements was acceptable and thus these judgements were included in the study. To a large extent, the local ranks for individual and group judgements were similar. Interestingly, group judgements were in a significantly smaller range than individual judgements. According to our data, the ranks of the criteria differed slightly according to the data aggregation method used. CONCLUSIONS: It is important to explain and justify the choice of an appropriate method for data acquisition because response behaviors differ according to the method. We conclude that researchers should select a suitable method based on the thematic perspective or investigated topics in the study. Because the arithmetic mean is very vulnerable to outliers, the geometric mean and the median seem to be acceptable alternatives for data aggregation. Overall, using the AHP to identify patient priorities and enhance the user-friendliness of information websites offers an important contribution to medical informatics.

Applying the Analytic Hierarchy Process in healthcare research: A systematic literature review and evaluation of reporting.

BACKGROUND: The Analytic Hierarchy Process (AHP), developed by Saaty in the late 1970s, is one of the methods for multi-criteria decision making. The AHP disaggregates a complex decision problem into different hierarchical levels. The weight for each criterion and alternative are judged in pairwise comparisons and priorities are calculated by the Eigenvector method. The slowly increasing application of the AHP was the motivation for this study to explore the current state of its methodology in the healthcare context. METHODS: A systematic literature review was conducted by searching the Pubmed and Web of Science databases for articles with the following keywords in their titles or abstracts: "Analytic Hierarchy Process," "Analytical Hierarchy Process," "multi-criteria decision analysis," "multiple criteria decision," "stated preference," and "pairwise comparison." In addition, we developed reporting criteria to indicate whether the authors reported important aspects and evaluated the resulting studies' reporting. RESULTS: The systematic review resulted in 121 articles. The number of studies applying AHP has increased since 2005. Most studies were from Asia (almost 30%), followed by the US (25.6%). On average, the studies used 19.64 criteria throughout their hierarchical levels. Furthermore, we restricted a detailed analysis to those articles published within the last 5 years (n = 69). The mean of participants in these studies were 109, whereas we identified major differences in how the surveys were conducted. The evaluation of reporting showed that the mean of reported elements was about 6.75 out of 10. Thus, 12 out of 69 studies reported less than half of the criteria. CONCLUSION: The AHP has been applied inconsistently in healthcare research. A minority of studies described all the relevant aspects. Thus, the statements in this review may be biased, as they are restricted to the information available in the papers. Hence, further research is required to discover who should be interviewed and how, how inconsistent answers should be dealt with, and how the outcome and stability of the results should be presented. In addition, we need new insights to determine which target group can best handle the challenges of the AHP.

Stereotactic radiosurgery for the treatment of brain metastases.

BACKGROUND: The objective of this systematic review was to summarise the current evidence concerning radiosurgical treatment (SRS) of newly diagnosed brain metastasis and to compare SRS as a single or additional treatment to treatment alternatives with regard to medical effectiveness and safety. METHODS: A structured search of electronic databases was performed to identify relevant publications from 2002 through 2007. Studies targeting patients with brain metastases were included. Standardised quality assessment and data extraction were performed. RESULTS: Of 1496 publications, 16 studies were included. The mean survival in most studies was less than 12 months. There was evidence that SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in patients with single metastasis, this resulted in improved survival. There was inconclusive evidence when comparing SRS to WBRT, Neurosurgery (NS) or Hypofractionated Radiotherapy (HCSRT). The Quality of life (Qol) was not investigated. CONCLUSION: SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in certain patients, this resulted in improved survival. Methodologically rigorous studies are therefore warranted to investigate further treatment options, and in view of the poor prognosis, to investigate Qol and neurological functioning.

Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare.

BACKGROUND: Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. OBJECTIVES: To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology-specifically economic evaluation methods-in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. METHODS: An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. RESULTS: Three key topics were identified and prioritised for discussion-uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. CONCLUSIONS: ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access. CLASSIFICATION CODE: I.

[Comparative cost analysis of outpatient and inpatient rehabilitation for cardiac diseases]. / Kostenvergleichsanalyse der ambulanten und stationären kardiologischen Rehabilitation.

PURPOSE: : To examine costs of inpatient and outpatient rehabilitation for cardiac disorders from the perspective of a major statutory health insurance fund in Germany. METHODS: : A nationwide database from a major health insurance fund in Germany was used to evaluate all rehabilitation cases in 2005. In addition to all direct cost domains of the rehabilitation itself, costs incurred in the preceding and the following year for hospital treatment, drugs and physical therapy were analyzed. A cost-cost analysis in different institutional settings was chosen for the cost comparison of in- and outpatient rehabilitation. To minimize the influence of possible confounders, a statistical control system was implemented. RESULTS: : Mean costs were 2,006 Euros for inpatient rehabilitation and 1,502 Euros for outpatient rehabilitation. No systematic differences were identified between in- and outpatient rehabilitation in costs for drugs and physical therapy in the year preceding and the year directly following the rehabilitation. The costs for hospital treatment in the year before rehabilitation were higher in inpatient rehabilitation, whereas in the year after rehabilitation no differences between in- and outpatient rehabilitation were seen. CONCLUSION: : Assuming comparable medical outcome, outpatient rehabilitation seems to pose a superior alternative compared to inpatient rehabilitation from an economic perspective. Hence, from the perspective of the statutory health insurance, fostering a higher market share of outpatient rehabilitation may add to a better allocation of overall health-care resources.

Medical effectiveness and safety of conventional compared to laparoscopic incisional hernia repair: a systematic review.

BACKGROUND: Incisional hernias are a common complication following abdominal surgery and represent about 80% of all ventral hernia. In uncomplicated postoperative follow-up they develop in about 11% of cases and in up to 23% of cases with wound infections or other forms of wound complications. While conventional mesh repair has been the standard of care in the past, the use of laparoscopic surgery is increasing. It therefore remains uncertain which technique should be recommended as the standard of care. OBJECTIVES: To compare the medical effectiveness and safety of conventional mesh and laparoscopic incisional hernia repair. METHODS: A structured literature search of databases accessed through the German Institute of Medical Documentation and Information (DIMDI) was conducted. English and German literature published until August 2005 was included and their methodological quality assessed. RESULTS: The search identified 17 relevant publications and included 15 studies for final assessment. Among those were one meta-analysis, one randomized clinical trial (RCT) ,and 13 cohort studies. All studies suffered from significant methodological limitations, such as differences in baseline characteristics between treatment groups, small case numbers, and the lack of adjustment for relevant confounders. Overall, medical effectiveness and safety were similar for both surgical approaches. However, there was a trend towards lower recurrence rates, length of hospital stay, and postoperative pain as well as decreased complication rates for the laparoscopic repair in the majority of studies. The impact of the technique of mesh implantation and mesh fixation as well as the impact of certain patient-related factors was not systematically assessed in any of the studies. CONCLUSION: No conclusive differences could be identified between the operative techniques. There was, however, some evidence for a trend towards similar or slightly improved outcomes associated with the laparoscopic procedure. There remains an urgent need for high-quality prospective studies to evaluate this question conclusively.

Methods for determining cost-benefit ratios for pharmaceuticals in Germany.

The aim of this methodological paper is to summarize evidence on how to implement cost-benefit assessment according to the new German legislative framework (Competition Enhancement Act). Given the complexity of existing health policy frameworks within industrialised countries in adapting health economics in their respective regulatory scheme, no clear international scientific consensus on which health economic methods should be chosen for assessment can be determined. Nevertheless, a broad consensus on the internal properties of methods itself can be found. Based on these common international standards in methodology, this work provides a minimum catalogue of methods and criteria that meet legal and local German requirements with regard to specific factors of its health care system. Aside from categorising clearly defined standards (e.g., study forms, cost and benefit categories) the suggested catalogue specifies some intensively debated areas in Germany (e.g., the QALY, modelling, the perspective used in the assessment). After the proposition of certain methods the paper leads to a first recommendation of a detailed assessment-process itself specific for the German way in implementing cost-benefit ratios within regulatory decision making in Germany.